Figure 1. The cellular and molecular pathways relating to aging
and age-dependent diseases. At the molecular level, persistent DNA
damage response (DDR) leads to activation of the tumor suppressor p53,
which in turn activates p21 to initiate cell cycle arrest and induce the
senescent cells and apoptosis. The generation of ROS results in
mitochondria dysfunction inducing by excessive mutations of mDNA. The
internal and external stress triggers the formation of misfolded
proteins, and their accumulation contributes to ER malfunction.
Respiration declines as a result of mitochondria dysfunction and Insulin
resistance because of ER malfunction lead to metabolism alternation. The
disrupted process involves Sirt1, and AMPK inhibition that adversely
affecting lipid metabolism. Another pathway mediates SASP production
that invokes pro-inflammatory pathways resulting in a severe
inflammatory response. Excessive immune system activity and metabolic
dysfunction at the tissue level are considered as critical age-related
diseases promotors (Nah, Yuan, & Jung).
ETC (Electron transport chain); ROS (Reactive oxygen species); UPRer (ER
unfolded protein response); UPRmt (mitochondrial unfolded protein
response); AP-1 (activator protein-1); SASP (senescence-associated
secretory phenotype ); NDs (neurodegenerative diseases); CVDs
(Cardiovascular diseases).
Figure 2 The cytokines and chemokines-mediated inflammatory
cascades triggered by upregulation and downregulation of
pro-inflammatory cytokines and anti-inflammatory factors in age-related
diseases.